MICA/NKG2D-mediated immunogene therapy of experimental gliomas.
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MICA/NKG2D-mediated immunogene therapy of experimental gliomas. / Friese, Manuel A.; Platten, Michael; Lutz, Stefan Z; Naumann, Ulrike; Aulwurm, Steffen; Bischof, Felix; Bühring, Hans-Jörg; Dichgans, Johannes; Rammensee, Hans-Georg; Steinle, Alexander; Weller, Michael.
In: CANCER RES, Vol. 63, No. 24, 24, 2003, p. 8996-9006.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - MICA/NKG2D-mediated immunogene therapy of experimental gliomas.
AU - Friese, Manuel A.
AU - Platten, Michael
AU - Lutz, Stefan Z
AU - Naumann, Ulrike
AU - Aulwurm, Steffen
AU - Bischof, Felix
AU - Bühring, Hans-Jörg
AU - Dichgans, Johannes
AU - Rammensee, Hans-Georg
AU - Steinle, Alexander
AU - Weller, Michael
PY - 2003
Y1 - 2003
N2 - The failure of conventional cancer therapy renders glioblastoma an attractive target for immunotherapy. Tumor cells expressing ligands of the activating immunoreceptor NKG2D stimulate tumor immunity mediated by natural killer (NK), gammadelta T, and CD8(+) T cells. We report that human glioma cells express the NKG2D ligands MICA, MICB, and members of the UL16-binding protein family constitutively. However, glioma cells resist NK cell cytolysis because of high MHC class I antigen expression. Plasmid-mediated or adenovirus-mediated overexpression of MICA in glioma cells enhances their sensitivity to NK and T-cell responses in vitro and markedly delays the growth of s.c. and intracerebral LN-229 human glioma cell xenografts in nude mice and of SMA-560 gliomas in syngeneic VMDk mice. Glioma cells forming progressive tumors after implantation of stably MICA-transfected human LN-229 cells lost MICA expression, indicating a strong selection against MICA expression in vivo. Rejection of MICA-expressing SMA-560 cells in VMDk mice resulted in protective immunity to a subsequent challenge with wild-type tumor cells. Finally, the growth of syngeneic intracerebral SMA-560 tumors is inhibited by peripheral vaccination with adenovirus-mediated, MICA-infected irradiated tumor cells, and vaccination results in immune cell activation in the NK and T-cell compartments in vivo. These data commend MICA immunogene therapy as a novel experimental treatment for human malignant gliomas.
AB - The failure of conventional cancer therapy renders glioblastoma an attractive target for immunotherapy. Tumor cells expressing ligands of the activating immunoreceptor NKG2D stimulate tumor immunity mediated by natural killer (NK), gammadelta T, and CD8(+) T cells. We report that human glioma cells express the NKG2D ligands MICA, MICB, and members of the UL16-binding protein family constitutively. However, glioma cells resist NK cell cytolysis because of high MHC class I antigen expression. Plasmid-mediated or adenovirus-mediated overexpression of MICA in glioma cells enhances their sensitivity to NK and T-cell responses in vitro and markedly delays the growth of s.c. and intracerebral LN-229 human glioma cell xenografts in nude mice and of SMA-560 gliomas in syngeneic VMDk mice. Glioma cells forming progressive tumors after implantation of stably MICA-transfected human LN-229 cells lost MICA expression, indicating a strong selection against MICA expression in vivo. Rejection of MICA-expressing SMA-560 cells in VMDk mice resulted in protective immunity to a subsequent challenge with wild-type tumor cells. Finally, the growth of syngeneic intracerebral SMA-560 tumors is inhibited by peripheral vaccination with adenovirus-mediated, MICA-infected irradiated tumor cells, and vaccination results in immune cell activation in the NK and T-cell compartments in vivo. These data commend MICA immunogene therapy as a novel experimental treatment for human malignant gliomas.
M3 - SCORING: Zeitschriftenaufsatz
VL - 63
SP - 8996
EP - 9006
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 24
M1 - 24
ER -
